scholarly journals Human recombinant erythropoietin improves motor function in rats with spinal cord compression myelopathy

2019 ◽  
Author(s):  
Takahiro Tanaka ◽  
Hidetoshi Murata ◽  
Ryohei Miyazaki ◽  
Tetsuya Yoshizumi ◽  
Mitsuru Sato ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Function ◽  
Motor Neurons ◽  
Spinal Cord Compression ◽  
Cord Compression ◽  
Anterior Horn ◽  
Cervical Cord ◽  
High Dose ◽  
Spinal Cord Tissue ◽  
Compression Myelopathy

AbstractOBJECTIVEErythropoietin (EPO) is a clinically available hematopoietic cytokine. The aim of this study was to evaluate the effect of EPO on a rat model of cervical cord compression myelopathy and to explore the possibility of its use as a pharmacological treatment.METHODSTo produce the chronic cervical cord compression model, thin polyurethane sheets were implanted under the C5-C6 laminae of rats and gradually expanded due to water absorption. In this model, motor functions significantly declined from 7 weeks after surgery. Based on the result, EPO administration was started 8 weeks after surgery. Motor function as seen with rotarod performance and grip strength was measured 16 weeks after surgery, and then motor neurons were stained with H-E and NeuN staining, and counted. Apoptotic cell death was assessed with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining. To assess transfer of EPO into spinal cord tissue, the EPO level in spinal cord tissue was measured with an enzyme-linked immunosorbent assay for each group after subcutaneous injection of EPO.RESULTSHigh-dose EPO (5000 IU/kg) administered from 8 weeks after surgery markedly restored and maintained motor function in the Compression groups (P < 0.01). EPO significantly prevented loss of motor neurons in the anterior horn (P < 0.05) and significantly decreased the number of TUNEL-positive apoptotic cells (P < 0.05). The EPO level in spinal cord tissue was significantly higher in the High-dose EPO group than other groups.CONCLUSIONSEPO improves motor function in rats with progressive chronic compression myelopathy. EPO protects anterior horn motor neurons and inhibits neuronal cell apoptosis in spinal cord compression. The neuroprotective effects can be produced through transfer of EPO into spinal cord tissue. These findings suggest that EPO has high potential as a treatment for developing compression myelopathy.

Cilostazol, a selective Type III phosphodiesterase inhibitor: prevention of cervical myelopathy in a rat chronic compression model

2014 ◽  
Vol 20 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Shinji Yamamoto ◽  
Ryu Kurokawa ◽  
Phyo Kim
Keyword(s):  
Spinal Cord ◽  
Grip Strength ◽  
Motor Neurons ◽  
Cervical Myelopathy ◽  
Cervical Spondylotic Myelopathy ◽  
Phosphodiesterase Inhibitor ◽  
Cord Compression ◽  
Anterior Horn ◽  
Cervical Cord ◽  
Forced Running

Object Regional blood flow is decreased in experimental models of chronic spinal cord compression, and the alteration presumably contributes to the development of myelopathy. Cilostazol (Otsuka Pharmaceuticals Co.), a selective Type III phosphodiesterase inhibitor, has been shown to be neuroprotective in cerebral hypoperfusion animal models and clinically effective in preventing the recurrence of cerebral infarction. To investigate the neuroprotective effect of cilostazol on cervical spondylotic myelopathy, the preventive effect against progressive motor dysfunction and the loss of anterior horn motor neurons were assessed using a chronic cord compression model in rats. Methods To produce chronic cervical cord compression in male Wistar rats, thin polyurethane sheets (3 × 5 × 0.7 mm) that gradually expand over 48–72 hours by absorbing water were implanted under the C5–6 laminae. In sham operations, the sheets were momentarily placed and then immediately removed. This model has been shown to reproduce characteristic features of clinical cervical myelopathy, with progressive motor disturbances after a latency period and insidious neuronal loss preceding the onset of symptoms. In the treatment group, cilostazol (30 mg/kg/day) was orally administered to the rats once a day, starting the day after surgery and continuing through the entire observation period of 25 weeks. In the control group, vehicle solution was administered under the same protocol. Changes in motor function were monitored by measuring bilateral forepaw grip strength and the duration of forced running on a treadmill. Twenty-five weeks after surgery, cervical spinal cords were examined histopathologically. Results Cilostazol preserved both forepaw grip strength and forced running capability. The drug also preserved anterior horn motor neurons in the C5–6 spinal cord segment, which diminished in number in the untreated chronic compression group. The drug decreased the number of TUNEL-positive apoptotic cells. Conclusions These results indicate that cilostazol is neuroprotective in the chronically compressed cervical cord and is potentially useful in the treatment of cervical spondylotic myelopathy.

Incidence, Presentation, and Outcome of Spinal Cord Disease in Children With Systemic Cancer

PEDIATRICS ◽  
1986 ◽  
Vol 78 (3) ◽  
pp. 438-443
Author(s):  
Donald W. Lewis ◽  
Roger J. Packer ◽  
Beverly Raney ◽  
Ihor W. Rak ◽  
Jean Belasco ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Delayed Diagnosis ◽  
Cord Compression ◽  
High Dose ◽  
Spinal Cord Disease ◽  
Satisfactory Outcome ◽  
First Relapse ◽  
Age Range ◽  
Neurologic Emergency

During a 40-month period, in 24 of 643 (4%) newly diagnosed patients with systemic cancer younger than 18 years of age (range: 3 months to 17 years) spinal cord disease developed. Patients with spinal cord disease included 21 children with metastatic spinal cord compression, two with treatment-related transverse myelopathies, and one with an anterior spinal artery stroke. Spinal cord disease occurred in 13 of 102 children (12%) with sarcomas, six of 82 (7%) with neuroblastomas, and four of 94 (4%) with lymphomas. Spinal cord compression occurred as the presenting sign of malignancy in six children (four with sarcomas and two with lymphomas). In the remaining 15 patients, cord compression occurred a median of 13 months after initial diagnosis, and in four patients it occurred at the time of first relapse. Symptoms of metastatic cord compression included back pain in 17 patients (80%), weakness in 14 (67%), sphincter dysfunction in 12 (57%), and sensory abnormalities in three (14%). Findings on plain radiographs of the spine were abnormal in only seven of 20 patients with cord compression, and myelography was needed to differentiate compression from other causes of spinal cord disease. Treatment included high-dose corticosteroids followed by operation (seven patients) or radiotherapy (14 patients). After treatment, nine of 15 nonambulatory patients became ambulatory, and five of 10 incontinent patients regained sphincter control. None of the patients with nonmetastatic spinal cord disease had a satisfactory outcome. Incorrect and delayed diagnosis was frequent in children with spinal cord disease (median time from onset of symptoms to diagnosis, 2 weeks) and 12 children were paraplegic and ten had loss of sphincter control at diagnosis. Spinal cord disease is a relatively common neurologic emergency in children with cancer, especially in those with sarcoma, and requires immediate investigation and intervention.

scholarly journals Human recombinant erythropoietin improves motor function in rats with spinal cord compression-induced cervical myelopathy

PLoS ONE ◽  
2019 ◽  
Vol 14 (12) ◽  
pp. e0214351
Author(s):  
Takahiro Tanaka ◽  
Hidetoshi Murata ◽  
Ryohei Miyazaki ◽  
Tetsuya Yoshizumi ◽  
Mitsuru Sato ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Function ◽  
Spinal Cord Compression ◽  
Cervical Myelopathy ◽  
Cord Compression ◽  
Recombinant Erythropoietin ◽  
Human Recombinant Erythropoietin

Cerebrospinal fluid lactate and electrolyte levels following experimental spinal cord injury

1976 ◽  
Vol 44 (6) ◽  
pp. 715-722 ◽  
Author(s):  
Douglas K. Anderson ◽  
Leon D. Prockop ◽  
Eugene D. Means ◽  
Lawrence E. Hartley
Keyword(s):  
Spinal Cord ◽  
Cerebrospinal Fluid ◽  
Spinal Cord Compression ◽  
Cord Compression ◽  
Spinal Cord Tissue ◽  
Post Injury ◽  
Content Type ◽  
Protein Levels ◽  
Cord Injury ◽  
Csf Lactate

✓ Cerebrospinal fluid (CSF) lactate, sodium (Na+), potassium (K+), calcium (Ca++), magnesium (Mg++), and chloride (Cl−) levels were determined for 17 to 21 days following experimental spinal cord compression in cats. Laminectomies were performed at L-2 under general anesthesia with aseptic techniques. Paraplegia was produced by applying a 170-gm weight transdurally for 5 minutes. Significant increases in CSF lactate levels were observed on the first through ninth days post injury with peak levels (50% above normal) occurring at Day 5. The only significant postinjury CSF electrolyte changes were elevation in Ca++ concentration on Days 3, 9, 11, 13, and 15, elevation in K+ concentration on Days 9 and 11 and decline in Cl− levels on the first day. The CSF K+ increase probably reflected cellular loss of K+ from damaged tissue whereas the Ca++ rise may have resulted from increased CSF protein levels. The prolonged elevation of CSF lactate indicates that tissue hypoxia plays a role in spinal cord compression paralysis, and that there is a continuing hypoxia of metabolically active spinal cord tissue for several days post injury.

scholarly journals Corticosteroid Treatment for Metastatic Spinal Cord Compression: A Review

2017 ◽  
Vol 7 (3) ◽  
pp. 272-279 ◽  
Author(s):  
Gordon D. Skeoch ◽  
Matthew K. Tobin ◽  
Sajeel Khan ◽  
Andreas A. Linninger ◽  
Ankit I. Mehta
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Clinical Symptoms ◽  
Treatment Strategies ◽  
Cord Compression ◽  
Metastatic Spinal Cord Compression ◽  
Treatment Modalities ◽  
High Dose ◽  
Dexamethasone Treatment ◽  
Corticosteroid Administration

Study Design: Narrative review. Objective: Metastatic spinal cord compression (MSCC) is a very frequent complication among cancer patients. Presenting commonly as nocturnal back pain, MSCC typically progresses to lower extremity paresis, loss of ambulatory capabilities, and paraplegia. In addition to standard treatment modalities, corticosteroid administration has been utilized in preclinical and clinical settings as adjunctive therapy to reduce local spinal cord edema and improve clinical symptoms. This article serves as a review of existing literature regarding corticosteroid management of MSCC and seeks to provide potential avenues of research on the topic. Methods: A literature search was performed using PubMed in order to consolidate existing information regarding dexamethasone treatment of MSCC. Of all search results, 7 articles are reviewed, establishing the current understanding of metastatic spine disease and dexamethasone treatment in both animal models and in clinical trials. Results: Treatment with high-dose corticosteroids is associated with an increased rate of potentially serious systemic side effects. For this reason, definitive guidelines for the use of dexamethasone in the management of MSCC are unavailable. Conclusions: It is still unclear what role dexamethasone plays in the treatment of MSCC. It is evident that new, more localizable therapies may provide more acceptable treatment strategies using corticosteroids. Looking forward, the potential for more targeted, localized application of the steroid through the use of nanotechnology would decrease the incidence of adverse effects while maintaining the drug’s efficacy.

Cardiovascular response to experimental spinal cord compression

1973 ◽  
Vol 38 (3) ◽  
pp. 326-331 ◽  
Author(s):  
Eduardo E. Eidelberg
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Cardiovascular Response ◽  
Pressor Response ◽  
Blocking Agent ◽  
Cord Compression ◽  
Left Ventricular ◽  
Cervical Cord ◽  
Content Type ◽  
Ectopic Beats

✓ Anesthetized, and unanesthetized decerebrate, cats were used to study the arterial pressor response to spinal cord compression. To produce a cervical compression it was necessary that the cervical cord be functionally connected to the thoracic cord, pressor response by the reverse was not true. A pressor response above 200 mm Hg systolic was associated with electrocardiographic (EKG) signs of left ventricular overload and ventricular ectopic beats. These changes were not prevented by atropine, hexamethonium, or propanolol. Both the pressor response and the EKG abnormalities were prevented by an alpha-adrenergic blocking agent. The authors conclude that alpha-adrenergically mediated arterial vasoconstriction is the effector mechanism in the pressor response to increased intracranial pressure or cord compression.

scholarly journals Epidemiological study of cervical cord compression and its clinical symptoms in community-dwelling residents

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256732
Author(s):  
Toru Hirai ◽  
Koji Otani ◽  
Miho Sekiguchi ◽  
Shin-ichi Kikuchi ◽  
Shin-ichi Konno
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Clinical Symptoms ◽  
Cord Compression ◽  
Community Dwelling ◽  
Gait Disturbance ◽  
Cervical Cord ◽  
Cervical Cord Compression ◽  
The Relationship ◽  
Disc Level

Background Degenerative compressive myelopathy (DCM) is caused by cervical cord compression. The relationship between the magnitude and clinical findings of cervical cord compression has been described in the literature, but the details remain unclear. This study aimed to clarify the relationship between the magnitude and clinical symptoms of cervical cord compression in community-dwelling residents. Methods The present study included 532 subjects. The subjective symptoms and the objective findings of one board-certified spine surgeon were assessed. The subjective symptoms were upper extremity pain and numbness, clumsy hand, fall in the past 1 year, and subjective gait disturbance. The objective findings were: Hoffmann, Trömner, and Wartenberg signs; Babinski’s and Chaddock’s signs; hyperreflexia of the patellar tendon and Achilles tendon reflexes; ankle clonus; Romberg and modified Romberg tests; grip and release test; finger escape sign; and grip strength. Using midsagittal T2-weighted magnetic resonance imaging, the anterior–posterior (AP) diameters (mm) of the spinal cord at the C2 midvertebral body level (DC2) and at each intervertebral disc level from C2/3 to C7/T1 (DC2/3-C7/T1) were measured. The spinal cord compression ratio (R) for each intervertebral disc level was defined and calculated as DC2/3-C7/T1 divided by DC2. The lowest R (LR) along C2/3 to C7/T1 of each individual was divided into 3 grades by the tertile method. The relationship between LR and clinical symptoms was investigated by trend analysis. Results The prevalence of subjective gait disturbance increased significantly with the severity of spinal cord compression (p = 0.002812), whereas the other clinical symptoms were not significantly related with the severity of spinal cord compression. Conclusions The magnitude of cervical cord compression had no relationship with any of the neurologic findings. However, subjective gait disturbance might be a better indicator of the possibility of early stage cervical cord compression.

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